Synthesis and Antibacterial Potential of Novel Thymol Derivatives Against Methicillin-resistant and Pathogenic Bacteria

Overview

Journal Front Chem

Specialty Chemistry

Date 2024 Oct 31

PMID 39478990

Authors

Ashutosh Shahi

Rakshit Manhas

Srija Bhattacharya

Arti Rathore

Puneet Kumar

Jayanta Samanta

Manish Kumar Sharma

Avisek Mahapa

Prasoon Gupta

Jasha Momo H Anal

Affiliations

Soon will be listed here.

Abstract

The increasing threat of antibiotic resistance has created an urgent need for new antibacterial agents, particularly plant-based natural compounds and their derivatives. Thymol, a natural monoterpenoid phenolic compound derived from , is known for its aromatic and therapeutic properties, including antibacterial activity. This study focuses on synthesizing dihydropyrimidinone and dihydropyridine derivatives of thymol and exploring their antibacterial properties. The synthesized compounds were tested for their antibacterial potential against pathogenic microorganisms, specifically (Gram-negative) and methicillin-resistant (MRSA) (Gram-positive). Among the synthesized derivatives, compound 3i (ethyl 4-(4-hydroxy-5-isopropyl-2-methylphenyl)-2-imino-6-methyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate) exhibited the most promising antibacterial activity, with minimum inhibitory concentration (MIC) values of 12.5 µM against and 50.0 µM against MRSA. Additionally, compound 3i demonstrated a synergistic effect when combined with vancomycin, enhancing its antibacterial efficacy. The optimum fractional inhibitory concentration index (FICI) observed was 0.10 and 0.5 for MRSA and , respectively, in combination with vancomycin. analysis of the physiochemical properties of 3i indicated compliance with all drug-likeness rules. Furthermore, molecular docking studies revealed that compound 3i has a stronger binding affinity to the target protein than thymol, providing valuable insights into its potential mechanism of action.

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